title: Exploring 4-substituted-2-thiazolylhydrazones from 2-, 3-, and 4-acetylpyridine as selective and reversible hMAO-B inhibitors.
abstract: A series of 4-substituted-2-thiazolylhydrazone derivatives have been synthesized and tested in vitro for their human monoamine oxidase (hMAO) A and B inhibitory activity. Our findings confirmed that the substitution at C4 of the thiazole ring was important to obtain highly potent and selective hMAO-B inhibitors with IC50 values in the nanomolar range. Moreover, these derivatives were endowed with a reversible mechanism of enzyme inhibition. Molecular modelling studies were performed to rationalize the recognition of all inhibitors with respect to hMAO-A and -B isoforms.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy. paola.chimenti@uniroma1.it
authors.forename: Paola
authors.initials: P
authors.lastname: Chimenti
authors.forename: Anél
authors.initials: A
authors.lastname: Petzer
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.forename: Melissa
authors.initials: M
authors.lastname: D'Ascenzio
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D006835:Hydrazones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D011725:Pyridines / Q000737:chemistry*; D013997:Time Factors
chemical_list: D006835:Hydrazones; D008996:Monoamine Oxidase Inhibitors; D011725:Pyridines; D008995:Monoamine Oxidase
keywords: Acetylpyridine; Molecular modelling; Monoamine oxidase; Reversibility; Thiazole